PB2033: ADVANCED CHRONIC MYELOMONOCYTIC LEUKEMIA IN ELDERLY AND FRAIL PATIENTS MANAGED BY AZACITIDINE IN THE FIELD OF CLINICAL PRACTICE.
Authors: Pasquale Niscola, Carla Mazzone, Nicolina Rita Ardu, Laura Cesini, Marco Giovannini, Stefano Fratoni, Paolo de Fabritiis
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: Chronic myelomonocytic leukemia (CMML) is a rare aging-related clonal hematopoietic stem cell disorder with overlapping myelodysplastic and myeloproliferative features, characterized by clinical heterogeneity and a quite variable prognosis. For higher-risk patients, allogeneic stem cell transplantation (SCT) remains the only attempt to cure the disease. Hypomethylating agents, although do not modify the natural course of the disease having no impact on mutational allele burdens, may be used as a bridge to transplant in selected patients or as a measure to disease control in those who are managed with palliative and life prolonging intents. In the latter setting, azacytidine allowed for an overall response rates (ORR) of 40%–50% and complete remission (CR) rates of 7%–17% as well as median overall survival (OS) ranging from 12 to 37 months. Aims: To report our real-life and single center experience in this setting. Methods: The analysis was conducted on an intention to treat basis, regardless to the number of cycles of azacytidine and included 23 CMML (21 CMML-2, 1 CMML-1 with severe and symptomatic cytopenias and 1 with CMML-related oligoblastic AML) with a median age of 75 (62- 84) years. Results: Patients started azacytidine (75 mg/m2) for 7 days, including 2-days break (AZA 5-2-2) every 28 days, after a time interval from the CMML diagnosis of 3 months (1–18). The median number of azacytidine courses was 19 (2-41) without remarkable side effects. Twenty-two patients completed at least 4 courses, while the remaining 1 progressed to AML after the second cycle of treatment. Eight out of the 23 patients (35%) achieved complete remission (CR) and 9/23 (39%) a partial remission (PR) with an ORR of 74%; 6/23 (26%) patients presented a primary failure to azacytidine. Three (18%) out of 17 responders were transplanted for which their survival data were censored at the time of allogenic SCT. Therefore, the OS from the start of azacytidine was 18,3 months with a significant difference by comparing responders vs. non-responders (28 vs. 13 months, respectively, p=0,001). Overall, 21/23 (91%) patients deceased, of which 8/21 (38%) because of unrelated medical complications, whereas 13/21 (62%) progressed to AML: 3 primary failure and 10 responders after a median time of 14 (6-44) months. The OS of secondary AML patients was approximately 3 months. Summary and Connclusion: Despite the small number of cases, our experience reflected a daily clinical real-life treatment scenario, given the high proportion of very old and medically complex patients. With these limitations, our results are encouraging given an ORR of 72% by azacytidine, having this agent allowed for an effective bridge to SCT in about 13% of treated patients. Therefore, our observations confirm and reinforce existing real-life evidences on the safety and the efficacy of this agent, allowing the disease control in most comorbid, older and heavily pretreated CMML patients. However, the survival of treated patients was limited and high transformation rate to acute myeloid leukemia was observed in our experience. Therefore, future studies are highly awaited in this difficult group of patients in order to identify druggable molecular signatures by novel compounds able to target the disease clone as well as the development of innovative strategies aimed at widening the possibility of SCT for the highest number of patients. Keywords: Chronic myelomonocytic leukemia